Details for: PRDM8

Gene ID: 56978

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRDM8

Ensembl ID: ENSG00000152784

Description: PR/SET domain 8

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • rod bipolar cell CL0000751
    CSI 19.41
    rCSI 34.87%
    PRS 98.12
  • ON-bipolar cell CL0000749
    CSI 12.45
    rCSI 18.51%
    PRS 98.52
  • progenitor cell CL0011026
    CSI 7.82
    rCSI 16.63%
    PRS 97.9
  • OFFx cell CL4033036
    CSI 7.02
    rCSI 33.05%
    PRS 95.71
  • glial cell CL0000125
    CSI 6.34
    rCSI 24.14%
    PRS 97.48
  • interneuron CL0000099
    CSI 5.74
    rCSI 11.53%
    PRS 98.36
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 5.15
    rCSI 6.6%
    PRS 98.61
  • invaginating midget bipolar cell CL4033034
    CSI 4.99
    rCSI 29.5%
    PRS 96.22
  • ependymal cell CL0000065
    CSI 4.68
    rCSI 9.5%
    PRS 95.44
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 4.66
    rCSI 10.12%
    PRS 95.85
  • OFF-bipolar cell CL0000750
    CSI 4.58
    rCSI 6.26%
    PRS 98.45
  • retinal bipolar neuron CL0000748
    CSI 4.37
    rCSI 8.18%
    PRS 97.64
  • neural progenitor cell CL0011020
    CSI 4.11
    rCSI 18.09%
    PRS 95.81
  • cerebellar granule cell CL0001031
    CSI 4.01
    rCSI 5.89%
    PRS 97.87
  • cerebral cortex neuron CL0010012
    CSI 3.86
    rCSI 15.73%
    PRS 97.18
  • amacrine cell CL0000561
    CSI 2.54
    rCSI 7.37%
    PRS 97.46
  • GABAergic amacrine cell CL4030027
    CSI 2.49
    rCSI 8.54%
    PRS 96.03
  • glutamatergic neuron CL0000679
    CSI 2.45
    rCSI 5.04%
    PRS 95.59
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.78
    rCSI 4.33%
    PRS 96.57
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.67
    rCSI 5.99%
    PRS 96.93
  • flat midget bipolar cell CL4033033
    CSI 1.24
    rCSI 8.88%
    PRS 96
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.95
    rCSI 2.97%
    PRS 97.41
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.91
    rCSI 5.36%
    PRS 96.99
  • cone retinal bipolar cell CL0000752
    CSI 0.61
    rCSI 7.91%
    PRS 97.68

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRDM8](/details-gene/56978) (PR/SET domain 8) is a protein-coding gene located on chromosome 4q21.21. It encodes a member of the PRDM family of transcriptional regulators, which are characterized by the presence of a PR/SET domain and zinc finger motifs. Functionally, [PRDM8](/details-gene/56978) acts as a histone H3K9 methyltransferase and a transcriptional corepressor involved in chromatin-mediated gene silencing ([GO:0003714](https://www.ebi.ac.uk/QuickGO/term/GO:0003714), [GO:0046974](https://www.ebi.ac.uk/QuickGO/term/GO:0046974)). Expression data highlights its highly specific and significant role within the central nervous system, particularly in the developing and mature retina. It shows exceptional significance in various neuronal subtypes, most notably in `[rod bipolar cell](/details-cell/CL0000751)` and other retinal bipolar neurons, suggesting a critical function in retinal development, cell fate specification, and neural circuit organization. ## Cellular Roles and Expression Landscape The expression profile of [PRDM8](/details-gene/56978) strongly indicates a specialized role in the central nervous system, with a particular enrichment in the retina. **Overall**, the gene exhibits its highest significance in highly specialized retinal neurons. It is a top marker for `[rod bipolar cell](/details-cell/CL0000751)` (CSI: 19.41) and `[ON-bipolar cell](/details-cell/CL0000749)` (CSI: 12.45), as well as other bipolar cell subtypes such as `[invaginating midget bipolar cell](/details-cell/CL4033034)` and `[OFF-bipolar cell](/details-cell/CL0000750)`. This pattern suggests a fundamental role for [PRDM8](/details-gene/56978) in the function and/or development of the retinal circuitry responsible for processing visual signals. Beyond the retina, [PRDM8](/details-gene/56978) is also a significant marker in neural progenitor populations, including `[progenitor cell](/details-cell/CL0011026)` (CSI: 7.82), `[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)` (CSI: 5.15), and `[neural progenitor cell](/details-cell/CL0011020)` (CSI: 4.11). This is consistent with its function as a transcriptional repressor involved in cell fate decisions during neurogenesis. Its significance extends to other mature neuronal and glial cell types, such as `[interneuron](/details-cell/CL0000099)`, `[glial cell](/details-cell/CL0000125)`, and `[L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059)`, underscoring its broad importance in maintaining neuronal identity and function throughout the brain. ## Pathways and Molecular Function The molecular functions of [PRDM8](/details-gene/56978) are deeply rooted in epigenetic regulation and transcriptional control, which aligns with its cell-specific expression pattern. As a transcriptional corepressor with `[Histone h3k9 methyltransferase activity](/details-ontology/GO:0046974)`, it directly participates in `[Chromatin remodeling](/details-ontology/GO:0006338)` to establish repressive chromatin states, thereby silencing target genes. This activity is critical for developmental processes where precise gene expression timing is essential. Its annotated roles in `[Corpus callosum morphogenesis](/details-ontology/GO:0021540)`, `[Corticospinal tract morphogenesis](/details-ontology/GO:0021957)`, and `[Oligodendrocyte development](/details-ontology/GO:0014003)` are consistent with its high expression in various neural progenitor and glial cells. By regulating transcription, [PRDM8](/details-gene/56978) likely orchestrates the differentiation programs that give rise to these complex structures and cell types. Furthermore, its involvement in Reactome pathways such as `[Cell-cell communication](/details-pathway/R-HSA-1500931)` and `[Cell junction organization](/details-pathway/R-HSA-446728)` suggests that its downstream targets include genes that mediate the physical and functional connections between neurons, a process essential for building the neural circuits where it is most prominently expressed. ## Research Directions While the primary function of [PRDM8](/details-gene/56978) appears to be in neurodevelopment, its specific roles in disease and as a potential therapeutic target warrant further investigation. One study has noted its potential connection to early-onset Lafora body disease, a severe neurodegenerative disorder, suggesting its dysfunction could have pathological consequences [Link](https://doi.org/10.1093/brain/aws205). **Proposed Hypotheses:** 1. Given its exceptionally high CSI in multiple retinal bipolar cell subtypes, [PRDM8](/details-gene/56978) acts as a master transcriptional regulator that specifies the fate of retinal bipolar neurons during development by repressing alternative lineage programs (e.g., photoreceptor or amacrine cell fates). 2. Based on its function in transcriptional repression and its link to neurogenesis, loss-of-function mutations in [PRDM8](/details-gene/56978) may lead to neurodevelopmental disorders or increase susceptibility to neurodegeneration by failing to properly silence aberrant gene expression programs in mature neurons. **Experimental Approach:** To test the first hypothesis regarding its role in retinal cell fate specification, a powerful approach would be to use a human induced pluripotent stem cell (iPSC)-derived retinal organoid model. CRISPR-Cas9 could be employed to generate a [PRDM8](/details-gene/56978) knockout iPSC line. Upon differentiation into retinal organoids, single-cell RNA sequencing (scRNA-seq) could be performed at various time points to compare the developmental trajectories and final cell type proportions between wild-type and knockout organoids. This would reveal if the absence of [PRDM8](/details-gene/56978) leads to a reduction in bipolar cell populations and a corresponding increase in other retinal cell types, providing direct evidence for its role as a cell fate determinant. Immunohistochemistry for bipolar cell markers (e.g., CHX10, PKCα) would further validate these findings at the protein level. **Therapeutic Potential:** As an intracellular enzyme involved in chromatin modification, [PRDM8](/details-gene/56978) is not a conventional drug target for antibodies. However, its histone methyltransferase activity makes it potentially amenable to modulation by small molecule inhibitors or activators. If its dysregulation contributes to neurodegenerative diseases like Lafora body disease, restoring its normal repressive function through pharmacological activators could be a viable therapeutic strategy. Conversely, if its aberrant activity in a specific context (e.g., brain tumors) contributes to pathogenesis, targeted small molecule inhibitors could be developed. The high specificity of its expression to the nervous system suggests that systemic delivery of such molecules might have a relatively focused effect with fewer off-target toxicities in other organs.

Genular Protein ID: 2780701739

Symbol: PRDM8_HUMAN

Name: PR domain zinc finger protein 8

UniProtKB Accession Codes:

Q9NQV8 A8K7X2 Q6IQ36

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 4 Ensembl 3 ExpressionAtlas 1 GO 13 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22961547

Title: Early-onset Lafora body disease.

PubMed ID: 22961547

DOI: 10.1093/brain/aws205

Sequence Information:

  • Length: 689
  • Mass: 71663
  • Checksum: 4D8E3EA8B463682A
  • Sequence:
    • MEDTGIQRGI WDGDAKAVQQ CLTDIFTSVY TTCDIPENAI FGPCVLSHTS LYDSIAFIAL 
KSTDKRTVPY IFRVDTSAAN GSSEGLMWLR LVQSARDKEE QNLEAYIKNG QLFYRSLRRI 
AKDEELLVWY GKELTELLLL CPSRSHNKMN GSSPYTCLEC SQRFQFEFPY VAHLRFRCPK 
RLHSADISPQ DEQGGGVGTK DHGGGGGGGK DQQQQQQEAP LGPGPKFCKA GPLHHYPSPS 
PESSNPSAAA GGSSAKPSTD FHNLARELEN SRGGSSCSPA QSLSSGSGSG GGGGHQEAEL 
SPDGIATGGG KGKRKFPEEA AEGGGGAGLV GGRGRFVERP LPASKEDLVC TPQQYRASGS 
YFGLEENGRL FAPPSPETGE AKRSAFVEVK KAARAASLQE EGTADGAGVA SEDQDAGGGG 
GSSTPAAASP VGAEKLLAPR PGGPLPSRLE GGSPARGSAF TSVPQLGSAG STSGGGGTGA 
GAAGGAGGGQ GAASDERKSA FSQPARSFSQ LSPLVLGQKL GALEPCHPAD GVGPTRLYPA 
AADPLAVKLQ GAADLNGGCG SLPSGGGGLP KQSPFLYATA FWPKSSAAAA AAAAAAAAGP 
LQLQLPSALT LLPPSFTSLC LPAQNWCAKC NASFRMTSDL VYHMRSHHKK EYAMEPLVKR 
RREEKLKCPI CNESFRERHH LSRHMTSHN

Genular Protein ID: 2108126233

Symbol: Q05CA1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q05CA1

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 SAM 1 SUPFAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 425
  • Mass: 44870
  • Checksum: A0DEA580F9699C83
  • Sequence:
    • MEDTGIQRGI WDGDAKAVQQ CLTDIFTSVY TTCDIPENAI FGPCVLSHTS LYDSIAFIAL 
KSTDKRTVPY IFRVDTSAAN GSSEGLMWLR LVQSARDKEE QNLEAYIKNG QLFYRSLRRI 
AKDEELLVWY GKELTELLLL CPSRSHNKMN GSSPYTCLEC SQRFQFEFPY VAHLRFRCPK 
RLHSADISPQ DEQGGGVGTK DHGGGGGGGK DQQQQQQEAP LGPGPKFCKA GPLHHYPSPS 
PESSNPSAAA GGSSAKPSTD FHNLARELEN SRGGSSCSPA QSLSSGSGSG GGGGHQEAEL 
SPDGIATGGG KGKRKFPEEA AEGGGGAGLV GGRGRFVERP LPASKEDLVC TPQQYRASGS 
YFGLEENGRL FAPPSPETGE AKRSAFVEVK KAARAASLQE EGTADGAGVA SEDQDAGGGG 
GSSTP